The work presented in this research proposal is designed to aid in the development of methods for the treatment and prevention of arthristis following bacterial joint infection. The proposed research continues experiments showing that in infectious arthritis, proteoglycans are the primary targets of cartilage destruction. The Specific Aims of this research proposal are directed at two hypotheses: 1) if collagen degradation is prevented, cartilage repair can occur; 2) the primary cause of cartilage proteoglycan loss is due to a specific response of cartilage cells to a foreign stimulus. The experimental approach relies on the use of animal models, in vitro bacterial and cartilage cultures, analytical biochemical assays for quantitation of short term bacterial effects on cartilage. By quantifying collagen and glycosaminoglycans, the extent of degeneration caused by bacterial infections will be established. Using these changes as an assay, the ability of antibiotic treatment to block or reverse deleterious bacterial effects will be analyzed directly in in vivo animal models. More direct approaches to the possible mechanisms by which the bacteria cause cartilage destruction will be carried out in in vitro analysis. Clinical isolates of bacteria will be challenged by direct bacterial inoculation under varying conditions to characterize the effect of bacteria on the chondrocytes and surrounding matrix without participation of the immune system.